Interstate 20 (I-20) is the main east–west Interstate Highway in the state of South Carolina, linking the state with important transportation and business hubs to the north, west, and south, including Atlanta, Georgia; Charlotte, North Carolina ; Savannah, Georgia ; and Washington, D.C.. I-20 travels 141.51 miles (227.74 km) west to east, from the Georgia state line at North Augusta, through Columbia, to end at I-95 in Florence. Past I-95, the roadway continues as Interstate 20 Business for about two miles (3.2 km) to U.S. Route 76 (US 76), which goes to downtown Florence.

Interstate 77 (I-77) is a north–south Interstate Highway, extending 91.2 miles (146.8 km) in the state of South Carolina, from the southern terminus at an interchange with I-26 near Columbia, north to the North Carolina state line near Rock Hill and Charlotte, North Carolina.